ABSTRACT
Background. Fungal infections have been identified with or following SARSCoV-2 infection, most commonly COVID associated pulmonary aspergillosis. Cryptococcus species are ubiquitous in the environment and the third most common invasive fungal infection following Solid Organ Transplant (SOT). We describe four cases of concurrent or subsequent cryptococcal infection within 90 days following COVID-19 infection. Methods. We conducted a retrospective study of patients presenting with proven cryptococcosis either concurrently or within 90 days following COVID-19 diagnosis. Cases were identified March 2020 through May 2021. All were seen at the University of Alabama in Birmingham, a regional referral and comprehensive transplant center. Exemption for this review was approved by our IRB. Results. Four cases were identified, all were SOT recipients. Case details are provided in Table 1. No patients required ICU level care at any point. COVID-19 treatment included 10 days of increased steroids for 3 patients, remdesivir for 2, and 1 received no treatment for COVID-19. In contrast to the typical time-course for cryptococcal infection post-SOT (median time approx. 500 days post-transplant), three patients were greater than 2 years post-transplant and were without rejection or recent changes in immunosuppression. Patient 1 was less than 6 months post liver-kidney transplant and was diagnosed at time of admission with concurrent COVID-19 and cryptococcal pneumonia. Infection was disseminated in the other 3 cases including positive blood cultures in 2 patients and cryptococcal meningitis (CM) in 2 patients. CM cases presented later following COVID-19 and had the longest delay between symptom onset (headache, neurologic symptoms) and CM diagnosis. One patient had CM 8 years prior, but had done extremely well off fluconazole for over 6 years prior to this recurrence. All patients are doing well at most recent follow-up evaluations. Conclusion. We describe the first case series with a temporal association between SARS-CoV-2 infection and cryptococcosis. All cases were immunocompromised due to SOT. Some symptoms were attributed to post-COVID syndrome leading to significant delays in diagnosis for those patietns, highlighting the importance of considering this association for at-risk patients.
ABSTRACT
Purpose: The incidence, clearance and clinical expression of viremia post-Tx are heterogeneous, complicating prediction, prognosis and therapy. We postulated that variation viral presentation related to HLA type may inform understanding, and we used in silico methods to assess the MHC-peptide binding affinity for three important phylogenetically distinct viruses (SARS-CoV-2, CMV and BKV). Methods: Carrier frequencies for 11 HLA genes (HLA-A, B, C;DRB1, DRB3/4/5, DQA1, DQB1, DPA1, DPB1) were determined by NGS in 1150 renal transplant recipients. All FASTA-formatted viral protein sequence data from the NCBI RefSeq database were kmerized into 8-12 mers. Using netMHCpan, MHC-peptide binding affinities were predicted and affinity scores <500nM were included in the HLA allele rankings Results: A total of 206 Class I HLA alleles identified in 1150 patients exhibited population frequencies ranging from 0.09% to 30%. Within this repertoire, peptide binding varied dramatically identifying low-and high-affinity alleles for each of the three viral proteomes. Alleles with lowest binding propensity were specific to each virus (e.g. HLA-B∗46:01 for SARS-CoV-2, HLA-B∗51:05 for CMV and HLA-B∗15:08 for BKV). In contrast, alleles with the highest binding propensity were remarkably uniform for all 3 viruses (e.g. HLA-A∗02:11 top for all three virus proteomes). Sequence signatures for HLA isoforms in the same allele group defined high or low binding characteristics, the difference being conferred by as little as a single amino acid within the peptide binding region (e.g. HLA-B∗15:08 vs B∗15:03). Carrier rates for predicted SARS-CoV-2 susceptibility/resistance genes in the transplant population were observed to be similar to global population carrier rates (Fig 1). Conclusions: Evaluation of peptide binding provides a unique insight into viral recognition. If confirmed in our current proof-of-principle study comparing sequence and outcome in a large Canadian population, this data may offer a vital biomarker to define risk and treatment within conventional virological patient strata following transplant. (Figure Presented).